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PacBio Hopes to Increase Research User Base With Sequel System; Mount Sinai Among First Customers


This article us been updated to correct a statement about customers who have ordered the RS II platform.

NEW YORK (GenomeWeb) – Two weeks ago, Pacific Biosciences launched the Sequel System, a new sequencing platform it has been developing in partnership with Roche that offers higher throughput at a lower cost than the company's existing RS II instrument.

At the American Society of Human Genetics annual meeting in Baltimore last week, PacBio Chief Scientific Officer Jonas Korlach and Executive Vice President and Chief Financial Officer Susan Barnes offered additional insights into the design and roll-out of the new platform.

The underlying single-molecule real-time sequencing technology, including the chemistry, zero-mode waveguides, and data analysis, is the same for the Sequel and the RS II, but the optical architecture of Sequel is more integrated and "fundamentally scalable," Korlach said.

The RS II, he explained, uses far-field optics that involve long paths of light and a large number of laser "beamlets", which is the main reason for that instrument's large size. The Sequel, on the other hand, utilizes a proprietary undisclosed optical technology, which allowed the firm to shrink the footprint of the platform, which is about the size of a freezer/refrigerator combo, to a third of that of the RS II.

The Sequel also enables users to track all reagents and consumables, which are tagged, on the instrument, which will be helpful for future regulated sequencing, and several modules of the instrument can be pulled out for servicing.

Along with the Sequel, PacBio plans to release version 3.0 of its SMRT Analysis software suite, which will include enhancements to the Hierarchical Genome Assembly Process (HGAP) to allow for the assembly of diploid human genomes, improved circular consensus sequencing that results in higher accuracy, and better amplicon analysis. The software will use the BAM file format for all sequence data, replacing the current HDF5 format.

PacBio plans to post datasets generated on the Sequel from projects that could be useful to the research community but has no timeline for that yet, Korlach said.

Overall, the applications for the Sequel will be the same as for the RS II. While microbial genome sequencing is a more mature application, others, such as human genome sequencing, which will be substantially less expensive to perform on the Sequel, will possibly open new markets.

PacBio said it expects to ship about 10 Sequel systems this year, including several that will go to its partner Roche for assay development. The Icahn Institute for Genomics and Multiscale Biology at Mount Sinai's Icahn School of Medicine in New York, which is headed by former PacBio CSO Eric Schadt, is among the first early Sequel customers — the institute said on Twitter last week that it is "thrilled to get two of the first six Sequel systems."

Barnes said the company prioritized early Sequel customers who understand the technology well — as there might be initial glitches, especially on the software side — and who are willing to report on their experience at scientific conferences, for example the Advances in Genome Biology and Technology meeting in Orlando next February.

Overall, the company hopes the lower price of the Sequel — $350,000, about half that of the RS II — as well as a less expensive service contract will make it attractive to laboratories who could not afford the RS II. Korlach said the firm has already received emails from laboratories expressing an interest in the Sequel.

At present, PacBio has approximately 150 RS II instruments installed worldwide, with some customers having more than one system. 

As reported previously by GenomeWeb, consumables costs per SMRT cell will increase almost threefold on the Sequel but output per SMRT cell will go up about sevenfold, so per gigabase, sequencing on the Sequel should be about 2.5-fold less expensive in consumables costs than on the RS II.

There is currently no upgrade or trade-in program for existing RS II users in place, Korlach said, but PacBio plans to work with customers who have an RS II system on order. In any case, PacBio "will not leave the RS II behind", he said, and future improvements in the sequencing chemistry and other areas will be compatible with both systems.

Longer term, the Sequel platform is slated to reach the clinical market. Under its agreement with Roche, Roche will sell the platform for clinical research and, ultimately, in vitro diagnostic applications, while PacBio will sell it into all other markets, including "some aspects of clinical research," PacBio said.

Roche expects to launch the system commercially in the second half of 2016. Its instrument will use the same platform underlying the Sequel System but will have additional features "to address the needs of the clinical market, including validated workflows and kit configurations," according to PacBio. It will also be branded differently and have a different look and logo.

Already, Roche and PacBio have been collaborating closely in preparation for Sequel's launch. Project teams from both companies — located in California about 30 miles apart, in Pleasanton for Roche and Menlo Park for PacBio — have been meeting on a regular basis, and while Roche has been particularly helpful in the regulatory area, Korlach said, PacBio has been able to advise Roche on assay development, for example.